System for development of therapeutic drugs and procedures

ABSTRACT

The present invention relates to a device and method for delivering drugs or sending or receiving information to or from a lab test animal over a long period of time without having the cords attached to the animal tangle as it moves around in its enclosure.

COPYRIGHT NOTICE

This application is a Continuation of U.S. non-provisional patentapplication Ser. No. 13/593,802 filed on Aug. 24, 2012 and is includedherein in its entirety by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a method or system of performingexperiments and testing therapeutic drugs and experimental procedures ona test animal. In particular, the present invention relates to a systemfor delivering optical, fluid, and electrical neuronal data to and froma test animal and/or applying one or more procedures to the animal atthe same time while compensating for animal movement to prevent, overlong times, twisting of the cable connections for fluid exchange andsampling, optical or electrical connections. The system is designed forchronic application and implantation within an animal model (includinghuman) test subject. The system also defines a process and system forcreating therapies.

2. Description of Related Art

Multichannel microwire arrays, carbon fibers, microfabricated silicon orceramic electrode arrays for acquiring neural signals and chemicalsignals from large numbers of single neurons and from multiple brain orbody regions, and for stimulation of brain regions, are known in theart. Arrays usually comprise one or more microwires, multisite probeswith specialized chemical sensor sites, or carbon electrodes. One ormore connectors, flexible cable connectors with leads, or printedcircuit boards are in electrical connection with the electrodes. Theseconnectors are useful for studying higher order functions of the brainand actions of drugs in relation to behavior during stimuli which cannotbe determined with single or small numbers of neuronal connections. Thebrain and body consists of a complex biological system that requiresconcurrent observation and causal probing at many interconnected sitesto reveal function and to develop therapeutic strategies.

While this type of interface is capable of measuring very specificactivity of the brain during stimulation or behavioral constraints witha great deal of information being acquired or delivered, the ability todo so with a moving animal subject, such as a mouse or rat has beenlimited. Originally, the most common method of dealing with an awakeanimal during measurements was to restrain the subject to prevent themfrom disturbing contacts of probes with neurons, twisting theconnections, and thus, damaging the connections, the animal, or both.This makes long term studies very difficult to conduct and studies wherethe animal must move to create the stimulus is impossible. This is truefor all animal connections including optical, fluid, and electricalconnections.

The problem of allowing the animal to move freely while maintainingmultiple electrical including video, fluid, or optical connections isexacerbated by the need for a rotating swivel for each type ofconnection. Frequently, in the past, the problems with the addition ofmultiple connections to animals during testing was dealt with by use ofslip ring bushings which allowed the connecting lines to the highdensity array each to twist, thus, preventing twisted lines. However,for multiple animals, and in general, the slip rings are expensive touse and to coordinate, may introduce electrical noise, and therefore area problem of their own.

A similar problem applies to connections needed to control electricalstimulation in multiple areas such as the brain. Also difficult forthese reasons is the use of multiple sensors that require a combinationof electrical stimulation and recording. Sensors of many types have thiscommon difficulty. These may include combinations of functions forelectrical recording, electrical stimulation, chemical sensing, pressuredetectors, movement and mechanical deformation sensors, opticalstimulation, optical sensing, video capture, sound sensing in theauditory range, ultrasound for imaging, stimulation, and fluid flowmeasurement. It is clear that the difficulties to be addressed arecommon to multiple sensor/stimulation systems that need to operate inparallel and that require connections to external instrumentation.Typically, the larger the numbers of connections and type, the moredifficulties arise.

Chronic dosing of an animal or sampling of body fluids by attachment ofmultiple fluid drug sources with a control to regulate the timing andamount of a delivered drug or obtaining a fluid sample is an evengreater problem. A rotatable fluid swivel connector is not a veryeffective means of delivering multiple types of fluid drug doses. Theyare cumbersome and it is difficult to prevent leaks with multiple fluidconnections. Accordingly, the combination of delivering drugs andsimultaneously performing multichannel array neuronal readings has beenalmost impossible to accurately and consistently accomplish over theperiods of time necessary to perform drug testing on animals withparallel behavioral assessment. Even further, research with this type ofmeasurement is limited at best and data is not useful enough to beconsistently accurate (see e.g. www.Instech.com). Use of lasers to applylight stimulation to multiple sites, and light sensors, scanners orimagers are also burdened with this problem.

Of great use would be a system that allows for administration oftherapeutic test drugs and other experimental manipulations whilemonitoring or stimulating neuronal activity and behavior throughmultiple modes involving fluids optically or electrically connecting toa moving animal that can easily be accomplished during tests over longperiods of time, and especially for simultaneous use with multipleanimals to achieve high throughput testing for development of therapies.

BRIEF SUMMARY OF THE INVENTION

The present invention relates to an animal testing system wherein theexperimental and therapeutic liquid sources, electrical connections forstimulation, optical stimulation and recording, and the circuit boardcontrolling flow of information from the connections are mounted on arotating platform positioned over an animal chamber, thus, allowing thecircuit board, fluid containers, and other devices to be rotated withthe animal rather than the connections being rotated. The rotation isaccomplished by use of movement detectors which input animal movement toa circuit board, and thus can cause the platform to be rotated incoordination with the animal movements. Tangling and other problems ofthis type of testing are avoided and long term animal studies can beaccomplished with this system. Small electronic parts and computerprocessor boards are utilized so that inertia can be overcome and sothat all operating parts can rotate with the animal.

Accordingly, in one embodiment of the present invention, there isdisclosed an animal test system for use with a moving tethered testanimal comprising:

-   -   a. an animal chamber having a bottom surface for containing the        test animal;    -   b. a rotating platform positioned above the animal chamber        bottom;    -   c. a motor for rotating the platform clockwise or        counterclockwise;    -   d. at least one connector for a tethered connection to the        animal for delivering or receiving at least one of optical,        electrical, or fluid connection to the animal wherein an        opposite end of the connection is positioned on the platform;    -   e. one or more movement sensors positioned near the connector or        in the chamber to sense the movement of the animal in the        chamber wherein the sensors are used to send movement data to a        digital feedback system which controls the motor to rotate the        platform clockwise or counterclockwise based on the animal        movement sensed in a manner to prevent unwanted twisting of the        animal tethered connection; and    -   f. a digital data system in digital communication with the        connection to the animal.

Yet another embodiment comprises a method for testing a drug in one ormore animals positioned in an animal chamber comprising:

-   -   a. positioning a motorized rotating platform above a floor of        the chamber;    -   b. placing a desired quantity of the drug in liquid form in a        drug delivery container, positioning the container on the        platform, and creating a tethered connection of the drug        container to the animal;    -   c. positioning one or more movement sensors to sense the        movement of the animal in the chamber which can control a motor        to rotate the platform clockwise or counterclockwise based on        the animal movement sensed in a manner to prevent unwanted        twisting of the animal connection to the drug container;    -   d. delivering the drug to the animal;    -   e. optionally sampling fluids from the animal's brain or body in        a desired manner; and    -   f. monitoring the results of the administered drug while        rotating the platform to account for the animal movement.

An important feature of one embodiment is that data collection from theanimal is done by a computer, with disk storage or other digitalcollection system that also rotates with the animal though it could beremote or particularly on the system and particularly of the system. Thecollection system and all other devices receive power through a set ofslip rings. Data are transmitted from the rotating unit by one or moremeans including wireless transmission, optical rotating commutators, orthe like. Time synchronizing pulses are connected to the digitalcollection system via a slip ring, high speed wireless, optical links,or the like.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a relationship chart of an embodiment of the presentinvention.

FIGS. 2 a, 2 b, and 2 c depict embodiments of the platform and means forrotating the platform.

FIG. 3 is a perspective view of a rod and slot movement sensor.

FIG. 4 is a perspective view of an embodiment of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

While this invention is susceptible to embodiment in many differentforms, there is shown in the drawings and will herein be described indetail specific embodiments, with the understanding that the presentdisclosure of such embodiments is to be considered as an example of theprinciples and not intended to limit the invention to the specificembodiments shown and described. In the description below, likereference numerals are used to describe the same, similar orcorresponding parts in the several views of the drawings. This detaileddescription defines the meaning of the terms used herein andspecifically describes embodiments in order for those skilled in the artto practice the invention.

Definitions

The term “about” means ±10 percent.

The term “essentially” means ±10 percent.

The term “comprising” is not intended to limit inventions to onlyclaiming the present invention with such comprising language. Anyinvention using the term comprising could be separated into one or moreclaims using “consisting” or “consisting of” claim language and is sointended.

The terms “a” or “an”, as used herein, are defined as one or as morethan one. The term “plurality”, as used herein, is defined as two or asmore than two. The term “another”, as used herein, is defined as atleast a second or more. The terms “including” and/or “having”, as usedherein, are defined as comprising (i.e., open language). The term“coupled”, as used herein, is defined as connected, although notnecessarily directly, and not necessarily mechanically.

Reference throughout this document to “one embodiment”, “certainembodiments”, and “an embodiment” or similar terms means that aparticular feature, structure, or characteristic described in connectionwith the embodiment is included in at least one embodiment of thepresent invention. Thus, the appearances of such phrases or in variousplaces throughout this specification are not necessarily all referringto the same embodiment. Furthermore, the particular features,structures, or characteristics may be combined in any suitable manner inone or more embodiments without limitation.

The term “or” as used herein is to be interpreted as an inclusive ormeaning any one or any combination. Therefore, “A, B or C” means any ofthe following: “A; B; C; A and B; A and C; B and C; A, B and C”. Anexception to this definition will occur only when a combination ofelements, functions, steps or acts are in some way inherently mutuallyexclusive.

The drawings featured in the figures are for the purpose of illustratingcertain convenient embodiments of the present invention, and are not tobe considered as limitation thereto. Term “means” preceding a presentparticiple of an operation indicates a desired function for which thereis one or more embodiments, i.e., one or more methods, devices, orapparatuses for achieving the desired function and that one skilled inthe art could select from these or their equivalent in view of thedisclosure herein and use of the term “means” is not intended to belimiting.

The present invention relates to a process which includes a system anddevice for preventing the tangling of any electrical, optical, or fluidcords or tubes connected by a connector to a moving animal or cageduring the medical testing of that animal. Data can be delivered to theanimal or received from an animal. Also, manipulations of the animal canbe done by any type of connectors. In one embodiment, the delivery oradministration of data or experimental manipulations is accomplished byuse of a multichannel microwire, multicarbon fiber, multisite silicon,ceramic electrode array, acoustic stimulation and recording, opticalstimulation and recording, dialysis administration and sampling offluids, or other sensors and actuators. These connections are controlledby a digital data system, such as a circuit board, a computer, acombination of the two, or any digital means to collect to administerdata to or from an animal. The multichannel microwire electrode array ora multisite silicon or ceramic probes are embodiments of the inventionused by inserting the array to individual neurons in the animal, or fromdifferent sites in the body, with an individual channel representingdata to or from an individual neuron or individual location for sensingvoltage. Connections to the animal for other uses could easily be madein view of this disclosure.

In other types of connections to the animal there would be a putativemedical treatment, such as a tube connected to an animal foradministration or sampling of a fluid containing molecules in solutionor suspension, such as a drug, blood, plasma, or the like; or thewithdrawal of an animal bodily fluid, such as brain or body interstitialfluid, blood, urine, or other liquid. The administration of a drug couldbe for use in testing the drug's efficacy, controlling the animal'sbehavior or physiological activity, affecting the neuronal data beingcollected, or the like. Bodily fluids could be received for the purposeof monitoring the animal during the testing of the animal by any means.Other animal connections could easily be determined and as long as theconnections are tube or cord like in shape and nature, they wouldclearly work with the present invention. Other forms of animalconnections might also work with the present invention and one facedwith a different animal connection could clearly tell if the presentinvention were appropriate or not, however, in general, flexibleconnection like cords and tubes would be the most common type ofconnection. Wireless or optical connections with the animal are also tobe used in the present invention, however, one would still utilize theposition of a digital data system on or near the platform.

As used herein “test animals” are animals such as mammals; such as,rats, mice, and humans; birds; reptiles; any other living being, or thelike, which have a tendency to move about in their cage in a manner thattangles any connection to the animal. Any animal that tolerates atethered connection can be used. The same principle could be applied toa human animal in a space when use of a tethered system is appropriateand mobility is desired. The animal tethered connections allow fortransfer of test data, fluid or optical connections, or any cable, tube,or the like connected to the animal during the testing of an animal in atest situation. The animals are normally in their own individualchambers. The chambers can be used to examine a wide range ofneurophysiological or body behaviors when devices for sensorystimulation, feeding, drinking, and a means for behavioral observationare provided.

Chambers of the present invention could be nothing more than a bottomsurface and sides (such as a box) with a top being optional if the sidesare tall enough. In one embodiment, the chamber could be a room. Anymaterial, such as metal, plastic, wood, or the like can be used. In oneembodiment, the chamber is a Plexiglas type material so that the animalcan easily be viewed without bars or the like obscuring the view of theanimal. The chamber can include just the connections to the animal wherethe system sits mostly (from the turning unit, for example) above thechamber or can include sides high enough to include the entire systeminside the chamber. One purpose of the chamber is to limit the movementarea of the animal. Another purpose is to make devices accessible forinteraction with the animal. A lever or photocell to detect movement orrotation of head position, a spout to drink fluid, and a trough or otherdevice to obtain food are useful devices for inclusion in the animalchamber. Accordingly, for the purposes of this invention, “chamber”shall also refer to any means or device which limits the travel area (afence or room, for example) of the animal during use of the system. Inone embodiment, the rotating system is on the ceiling and allows theanimal to roam within a large region, such as a room.

A “platform”, as used herein, refers to a relatively flat, i.e.,horizontal shelf of any desired shape (e.g. circular) for positioningelements of the system over the animal which benefits from being rotatedto prevent twisting of the connection to the animal wherein the otherend of the connection resides on the platform. The platform, forexample, could have one or more liquid containers designed fordelivering drugs or therapeutic modalities, one or more containers forcollecting liquids from the animal, one or more computers, circuitboards for partial control of the system or tests being conducted (forexample, to control release of a drug on a prescribed regimen), a devicefor collecting data from a multichannel microwire electrode array,timers, or any other chemical sensors, fluidic or optical device. Thesize and shape (overall dimensions) of the platform would be based onthe desired device or object placed on the platform, the weight ofobjects on the platform, and the exact position of the platform over theanimal. The platform could be square, round, polygonal, or the like asdesired and as thick or thin for the particular use and user. Otherconsiderations for size include if the platform is in the chamber thathas limited dimensions or above the chamber, thus, allowing fordimensions larger than the floor or horizontal dimensions of the chamberbelow it. The platform employs a bearing to support its weight and isrotatable by any convenient means, such as by a center post or rod thatis rotated or by a motor directly turning the platform itself. In oneembodiment, the platform has a vertical center post hanging from aboveattached to a bearing to support weight, and is rotated by attaching amotor to the center post and using a motor to spin the center post. Thiscould be done, for example, by attaching a motor to a belt drive andusing the belt and pulleys to spin the center post. Power is transferredto the rotating system by using a multiple contact commutator systemintegrated into the post. Alternately, power could be transferred usingcoils and induction methods to transfer between stationary and rotatingcomponents.

The platform, as mentioned above, could be positioned above the chamberor within the chamber as desired. However, the closer to the animal, theshorter the connection will be between the animal and anything on therotating platform. The platform could also have one or more holes forpassing the animal connections through from the top of the platform tothe animal underneath the platform. While the connections could be runover the edge of the platform holes near the center of the platformminimizing the distance, the connections need to run and provide lesstendency to kink and twist during use of the present invention.

As used herein a “motor” for rotating the rotating platform refers to anA/C or D/C motor with or without gears and pulleys which can rotate theplatform in both a clockwise and counterclockwise direction. Therotation would be in small increments designed to be just enoughrotation, such that as the animal turns in the cage, the platformrotates, thus preventing any connection to the animal from twisting orkinking. Accordingly, the motor must be able to engage and turn theplatform incremental portions of a full rotation or more as needed.Control of this process is further explained below. The motor can beattached to a central post which is capable of turning the rotatableplatform much in the manner that old phonograph turntables work with adrive belt attached to the drive shaft at the top or bottom and thelike. But any method of turning the turntable would be acceptable andone skilled in the art could devise any number of motors, belts, andgears that could turn the rotatable platform. Likewise, while theparticular embodiment depicted in the figures shows the motor at the topof the device, the motor could be located at any place convenient aboveor below the platform as designed given that there are a large number ofways to rotate things with motors. Again, one viewing the presentinvention would be able to figure other ways without undueexperimentation.

“One or more sensors” refers to a means for detecting the animalmovement, i.e. that the animal is turning in the cage and the ability tosend that information to the motor in such a way that the motor couldinterpret the movement and determine which way to rotate and by how muchas necessary. Sensors include photocells which could be triggered bymovement, IR detection, radar, global positioning, video analysis withtracking, and the like. In one embodiment, the sensor comprises a rodand slot detection system. A rod and slot system of detection attaches arod directly or indirectly to a cable from the animal, one end of therod is then positioned in a slot (rectangular square oval, evencircular, or the like). As the animal moves and causes twisting ormovement of the cable, so does the rod within the slot. When the animalmoves (for example, starts to rotate within the chamber) enough that therod touches an edge of the slot, the position of touching is detected byelectrical connection, magnetic switch, by breaking light path to aphotocell, switch, or other like connection, thus creating an indicationof where the animal is or in which direction and by how much the animalis rotating. Then a computer or other circuit, such as on the digitaldata system, can determine where the animal is and how much, if at all,the platform should be rotated to correct for animal movement. The rodhitting the left side or blocking light on the left photocell, forexample, might indicate the need for counterclockwise rotation whilehitting the right side would indicate a reverse direction is needed.Detection of torsion of the cable through change in resistance of anelement or change in magnetic field could achieve the same result. Theexact location in the slot would indicate how much rotation isnecessary, although a fixed amount could always be moved and then thesystem could reevaluate the animal position, and thus make a number ofcorrections as time passes. Photocells to detect the position of the rodare one other method. In general, if slot and rod, photocell, or anyother detection system is used, the rotating right and left based onpositioning of the animal is achieved by maintaining a digital feedbacksystem which can be on the digital data system or separate whichconstantly records and evaluates the animal position. One skilled in theart, in view of the present disclosure could easily and without undueexperimentation program a computer or the like to rotate the platformclockwise or counterclockwise in view of an animal position. The rod andslot detection system is an embodiment though that is simple and merelydetecting where in the slot, the rod has to hit and activate a switch orblock light to a photocell, and is a simple way of making such adetermination. The relation of the rotations of the animal connectionand the animal itself may change from animal to animal and connectiontype to connection type. No one particular system nor computation wouldsuffice, but again, those changes in the program rotation amount caneasily be built into the system, such that human or computer feedbackcan make corrections to the system that begins to over or under correctfor rotation of the animal versus the platform.

As used herein the “hanging side S suspension support” refers to onemethod of supporting the cables or tubes making animal connections tohelp keep small animal movements from creating kinks, folds, twists, andbends when the platform fails to rotate with the animal movements, andthus reducing the need to rotate the platform manually to unraveltwists. A tall chamber allows use of a larger area since simple rotationof the cable around the axis in the center at the top can be detected byalternate means. A cable with some stiffness is less prone to twistsince its rotation is readily detected at a distance.

Counterweighting the end of the cable at the animal allows the animal tolift a lighter weight when moving, and removes the slack that allowstwisting. The “hanging side S suspension” can be seen in FIG. 3described later. The “hanging side S suspension” represents an instanceof a class of physical arrangements of cable from the animal to the topof the chamber that is counter weighted to allow free movement of theanimal and minimizes the formation of twists that effectively shortenthe free cable. The “hanging side S suspension” allows use of a shorterheight from the animal to the top of the chamber. The side S takes aportion of the cable or tube and suspends it from above, and in oneembodiment to the bottom of the platform or otherwise, such that theconnection also gets rotated during use of the system. The connectionscan be suspended by cable, thread, cord, or the like, however, anyrelatively thin suspension device like polymeric thread of sufficientdiameter would be one embodiment. In this embodiment a nylon thread,such as fishing line, hangs from above the thin rod and is threadedthrough a hole in the rod which is offset from the axis of rotation. Itis attached to a loop in the cable so that small movements of theanimals will move the rod to block light to the photocell. As can beseen, the portion of the cable raised up is tied at the apex of thatportion. The side S suspension also takes weight off of the cable andanimal by providing an effective counter weight, and thus allows theanimal to have a heavier connection than would otherwise be usablewithout the side S suspension system. The hanging S configuration can beachieved by use of an arm with weight opposite the cable to provide offset and effectively lighten the descending cable. Installing themovement sensors directly above the animal minimizes the tendency tokink and twist the cable when the animal rotates. Stainless steelsprings protect the cable from damage, and use of multi-threaded silvercoated copper wire reduces electrical noise. Other configurations withother connection support could also be used as necessary to providesupport to the animal connections. It might also be noted that wheremultiple connections to the animal are used, for example, a multichannelarray and a fluid drug connection, that the cables and tubes can beconnected as if one cable, thus eliminating the need for multiplesuspension systems or the possibility of the multiple connectionsgetting tangled. In the case of a human animal, the Hanging-S class ofconnection could take the form of a hanging pole and platform withdevices, an equivalent to a platform on rotating wheels of coasters thatcan be made to rotate with a human when moving within a space.

As used herein “digital data system” is an embodiment of a computer orother like device for collecting data differentially from the animal. Inone embodiment the digital data system has a digital storage devicepositioned on the turn table. It can also refer to a data transfermethod with external controls. A set of rings with contacts providepower for all elements of the rotation system. Data transfer can includetransfer by wideband wireless, USB, or ultra wideband wireless, opticalcommunication, wired connection optionally utilizing a multiple contactcommutator system (including power transfer system). The system can beused for a number of processes in the present system to serve multiplechannels for sensors and stimulation. The digital data system cancollect and interpret data received from the animal, it can accuratelytime random events, and control the time of stimulation and release ofdrugs and other procedures used in the system. For example, when thereis a liquid drug solution syringe pump positioned on the platform, itcan control the time and amount of drugs depending on schedules andconditions. A second example is to control the patterns and timing ofelectrical or optical stimulation events. Computations for the rotationof the platform and the like can be done by the digital system. Thedigital data system can be a small circuit designed to perform limitedactivity, for example, rotation, data collection and drug delivery orcan be a field programmable gate array, digital signal processor,computer, a mini-super computer with operating system and components, aquantum computer, and combinations of these components or anycomputational machine. By choosing a large external computer to receivedata and send commands, multiple systems with multiple animals could beutilized with just a single computer to control other devices, archivedata and analyze data. At least, a portion of the digital data systemcould be positioned on the platform if such is small enough. However,where a larger computer is necessary, for example, when acquiring andstoring date on multichannel microwire electrode array type connections,chemical sensors, optical and fluidic devices, it might be necessary toposition portions of the entire system of the invention separate fromthe present invention platform. In such cases where separate portionsare necessary, a connector between the two is necessary as is a means ofaccurately synchronizing digital time clocks on or off the platform andpossibly leaving a portion on the platform between the two devices.Multiple computers or digital devices for chemical sensing,microfluidics control, imaging via ultrasound, fluid flow determination,and other functions could also comprise the digital data system.Miniaturization of components allows many functions to be achieved. Inthat case, since the connection to the animal must rotate, and yet stillbe connected to the computer, use of a component of a slip ringconnection can be used to provide time synchronizing event informationand data transfer. Data transfer can be achieve using a combination ofwireless network connections and wired connection using links of thecommutator system. Such a connection is simple to use when a centralvertical rod is used, and in one embodiment, it is placed at or near thetop of the rod wherein connections can be strung down the rod throughthe platform and to the animal. Slip rings with different designs can beused to transfer data but are fairly expensive per channel, however, andone utilizing the system where possible would minimize the use of sliprings to power transfer and essential control functions. Slip rings witha central hole in the center rod can also be used when a portion of therotating platform supports the fluid reservoir and pump system above theslip rings.

In order to utilize the present system in a method to develop therapy bytesting the effectiveness of a therapeutic drug or an experimentalprocedure in an animal positioned in an animal chamber, there are anumber of steps utilized which could not effectively be accomplishedprior to the present invention. Once an animal is placed in the chamberof the system, the animal is connected to a drug delivery container witha means of dosing or stimulating the animal with a specific dose orstimulation pattern and a device to control the timing of suchprocedures. (General procedures of all types apply here—electrical oroptical stimulation, behavioral training, etc.) Once the animal isconnected to the drug delivery tubes of the system, the computer dosesthe animal or samples fluids at the predetermined intervals. Theplatform rotates clockwise and counterclockwise to prevent the tube ofdrug from kinking, and thus preventing dosages not reaching the animalwhen there is no attendant to watch the animal. Where there is amultichannel microwire electrode array, silicon or ceramic based array,other electrical or optical types of connections attached to the animal,the animal can be dosed and the effect on the animal measured. Forexample, a drug affecting neuronal processing could be administered andthen the multichannel microwire electrode array (or other recordingsensors and single or multi site probes systems) measure changes in theneuronal output, record it on a computer (digital data system),correlate with behavior and body physiology, and analyze the data.Because drug testing (and other procedures requiring measurement)usually happens over long times, at time days, weeks, or months, andbecause normally an animal would rotate and move so much during thattime, the connections would be impossible to keep during an entire testwithout constant observation. The present invention provides a means oftesting animals over long times, not before possible.

The system arrangement has the advantage of enabling multiplecapabilities by using combinations of configurations for many differentpurposes. One embodiment deals with applications requiring electricalstimulation to activate brain or muscles by using electrodes optimizedfor high current flow. This is often achieved through use of platinumiridium wires or with surfaces coated with activated iridium oxide tomaximized current flow for a given applied voltage. Multiple electricalconnections are required to apply voltage to alternate stimulationsites. The rotating electronics system allows many sites to be selectedand stimulated without need or limitation of multiple connectionsthrough rotating of commutator connections.

Another embodiment will employ one or more disposable or rechargeablebatteries to power devices that rotate with the system to provide powerfor the computer and other circuits. Power will be provided to wirelessdevices to transmit data to external computers.

One embodiment of the invention enables analysis of multiple fluidsamples to be acquired through use of micro dialysis probes. In thistechnique a small diameter u-shaped tubes made of a semipermeablemembrane is inserted into brain or body tissue. Fluids are pumped slowlyinto the sampling u-shaped micro dialysis tubes using stepper motorsystems to advance one or more fluid containing syringes. Drugs insidethe tube may diffuse through the membrane into brain or body tissues toexpose the tissue to a form of treatment or test. Alternately moleculesof interest can diffuse from the tissue through the membrane into thelumen of the tube. Fluid may be collected by the distal end of the tubethat extends above the animal to the rotating platform. Fluid exitingthe tube can be collected for later analysis by instrumentationspecialized for certain measurements. Alternately, the computer systemwith other circuits that rotates in parallel with movements of theanimal in the chamber may control appropriate devices and sensors inorder to perform tests in real time for presence and amount ofmolecules.

One embodiment uses a micro dialysis membrane to extract fluidcontaining dissolved ethanol from the body to follow the amount consumedand metabolized. Chemical tests then will determine presence and amountof ethanol in fluid exiting the return tube. Current generated byoxidation and reduction at an electrode will measure ethanolconcentration directly. Alternately, a decrease in oxygen concentrationin the fluid can be detected by an electrochemical sensor when theenzyme, alcohol dehydrogenase with ethanol and nicotinamide adeninedinucleaotide and ethnao as reagents, results in a product detected bycolorimetric methods. Colorimetric tests based on other enzymes andsubstrates can be used. The use of computer instrumentation of smallsize on the rotating platform enables multiple dialysis fluid tubes tobe employed and without need of a fluid swivel and with the advantage ofa shorter length of tubing from the subject to the instrumentation foranalysis.

Another embodiment uses antibodies that are specific for molecules ofinterest to be bound onto micro beads or nanoparticles suspended withinthe fluid flowing inside the micro dialysis tube. This arrangementcaptures specific molecules that diffuse from brain or body through themembrane to the suspended nanoparticles. Light is used to illuminatefluorescent molecules bound to the antibodies. Lenses and imagingsensors are used to image and measure optically the light intensity fromthe surface of the micro beads or nanoparticles. Images of the particlesare scanned with software within the field programmable gate arrays andhost computer to count particles and the intensity of emitted light toassess the presence and concentration of molecules of interest. In thisway the presence and concentration of molecules within brain tissues areassessed to enable development of therapies. One or more of such systemscan be combined with other devices rotated with the subject.

Another embodiment employs a large number of possible systems forchemical testing to be installed in the rotating system that would bemade functional by the capability of controlling fluid flow using pumps,and with the ability to insert robes with arrays of specific chemicalsensor site configured to detect different molecules. Chemical testingis made possible through the ability to perform electrochemicalmeasurements of chemical reaction products, and with the use of lightsources, optical sensors and imaging systems.

Further embodiments may employ one or more sensors includingthermocouples, thermistors, strain gauges, proximity sensors, lightemitting diodes to indicate position, acceleration rotation, andvelocity, stretch, temperature, blood flow, detection, electricalactivity of heart muscle and brain, and other parameters to determinebody function. Sensors and actuators to create ultrasound images andultrasonic sensors to detect fluid and blood flow will be used in therotating configuration.

Another embodiment will use one or multiple light sources to activateoptically active molecules and devices to stimulate biologicalprocesses. This configuration will be used to activate proteins thatincrease ion flow through neuronal membranes which then cause excitationor inhibition of neurons actions. This configuration would be useful toactivate or release caged or bound compounds to release molecules withactions for investigating therapeutic effects of molecules andtreatments.

Another embodiment will use one or more combinations of multiple lightsources and light sensors, imagers, scanners, lenses, filtercombinations, acoustic, and cameras to capture optical images from bodyparts or images of the surroundings of the subject. One or moremicroscopic images can be obtained of light or fluorescent images oftissues and cellular components.

Another embodiment will provide power to enable actuator and sensorcomponents for one or more ultrasonic imaging units to capture images ofbody components in behaving animals either alone or in combination withother sensors or stimulation units.

Multiple simultaneous observations can be made possible of brain, heartand tissue activity.

Now referring to the drawings for one embodiment of the presentinvention. FIG. 1 is a relationship chart of the elements of anembodiment of the present invention. This figure depicts an embodimentwith an animal having both a multichannel microwire electrode arrayconnection, an optical, and a fluid drug connection. In FIG. 1, animalchamber 1 contains animal 2. Animal 2 has sensors, microwire or probeimplant, electrical recording, stimulation or electrochemical sensorsites, or optical 3, and fluid connections 4 to or from the animal 2.The multiple sensor or implant could be neuronal or other types ofconnections as noted in the general description.

Movement and rotation of the animal is detected by a sensor which causesrotation of the system connected to the animal 2. One instance of therotation sensor consists of a rod or tab 5 a and device with slot 5 b.Movement of the rod 5 a in either direction blocks one of two photocellswhich activates movement of the rotating system in a direction to followthe movement of the animal. The rod can be placed near the top of a tallhanging version of the cable system, or moved by a swinging movement ofa wire positioned to hold up the cabling system. Signals from the rod 5a and slot position detector 5 are sent to motor activation circuits orthe PC control board 15 via wire 14 which then sends a signal to themotor via wire 14 a. In other embodiments, the sensor may be a videotracker or is directly connected to the motor. The slot and rod deviceis described in more detail in FIG. 3.

Positioned above the animal chamber 1 is rotating platform 10. Sittingon rotating platform 10 is liquid source 11 which supplies fluid to theanimal 2 via. In this embodiment the multichannel microwire electrode orsensor array is connected via PC control board 15 along connecting wires16. The PC control board 15 is connected to a PC 17 for collection ofdata via slip ring 18. The PC control board 15 and PC togetherconstitute the digital data system. A motor 19 is positioned to rotatethe platform 10 clockwise and counterclockwise. The slip ring 18 rotateswith the platform 10 and keeps a connection of the PC control board 15to the PC for collection of data. In other embodiments, there is no PCcontrol board and all computer based connections are through the PC 17and slip ring 18 connection down the wires 16 to animal 2. In otherembodiments, there is no PC and only digital data system on theplatform.

FIGS. 2 a, 2 b, and 2 c depict embodiments of the rotating platformwherein there is hole 20 in roughly the center of the platform 10. Theliquid tube 12 and control board wiring 16 are fed through hole 20 anddown to the animal as shown in other figures. Other tethered connectionscan be utilized in this manner. In the side view of 2 b, the tubing andwiring can be seen passing through the platform 10. A ball bearingturntable 26 has platform 10 sitting on it while the turntable 26 restsin this embodiment on roof of chamber 27. The turntable 26 in thisposition also allows support to the platform and everything on theplatform 10 such that less effort is needed to turn the platform 10 bythe motor and more items can be placed on platform 10. In FIG. 2 canother alternative method of rotating where a support disc is shownsupporting a platform and is bolted to shaft 45, and the shaft supportsone or more platforms from above.

FIG. 3 shows a side view of the rod and slot position sensor of theinvention as well as an embodiment of the side S hanging connectionsupport. Fluid connection tube 12 is shown in S configuration 31 havingvalley 32 and mountain 33 portions of the hanging connection 31. Ahanging thread 35 connects tube 12 at the mountain point 33 up and hangsfrom the bottom of the rod and slot device 5. Movement of the animalmoves the S shaped cable, which moves the hanging thread, which movesthe rod to break the path between the light source and photocell, whichactivate circuits that cause movement of the motor that rotates theplatform. In this case, the sensor will rotate with the platform 10. Inother embodiments, the thread could attach directly to the platform 10.It is understood that the connection should be such that it rotates insync with the platform as described above.

FIG. 4 depicts a more detailed embodiment of the present invention. Inthis embodiment, motor 19 attached to motor support 19 a drives gear 40in both a clockwise and counterclockwise manner. In one embodiment, themotor support 19 a could be attached to chamber top wall 50. In otherembodiments, the motor 19 is fixedly attached to a wall or otherstationary item. A belt 41 is connected to the motor gear 40 and to apulley on the vertical rod gear 42. Vertical rod gear 42 is connected tovertical rod 45. The rotation of gear 40 in a clockwise orcounterclockwise direction causes vertical rod gear 42 to spin in thesame manner. Thus, the spinning of vertical rod gear 42 causes thevertical rod 45 to spin in tandem with the vertical rod gear 42. Therotation clockwise or counterclockwise of the vertical rod 45 causeseverything attached to the rod 45 to rotate in tandem with the rod 45.

In this embodiment, three items are attached to and rotate with thevertical rod 45. A slip ring 18 is affixed to the vertical rod 45. Asthe slip ring 18 rotates, brushes 52 make and maintain contact, thusallowing power to be transferred to all devices that rotate and datareceived from cable 16 to be transferred to the computer 17 via cable 17a. Platform 10 is located on chamber top 27 and is connected to verticalrod 45. Platform 10 also rests on turntable 26 (not seen in this view,but seen in FIG. 2 b) which rests on chamber top 27, thus the platform10 is supported by its connection to the rod 45 and it is resting onturntable 26. In this view, three holes 20 are shown. Instead of thembeing in the center of platform 10, they are shown a short distance fromvertical rod 45. Cables 12 and 20 are shown threaded through holes 20.Lastly, at the bottom portion of rod 45, there is shown rod and slotdetector 5 which is shown to also have holes 60 for further threadingthe cables. Note that the sensor 5 rotates with the animal and has thecable suspension 35 attached to a bottom portion much like in FIG. 3.

When animal 2 moves around, the cables move with the animal causingmovement rod 5 a to move within slot 6. When sides 30 are touched, byrod 5 a then a signal is sent to motor 19 to rotate the vertical rod tocompensate for the movement of the animal 2. The amount of movement iscalculated by a digital feedback system on the PC control board 15, thePC 17, or any other device placed in the system for calculating themovement required to compensate for movement of animal 2. In this view,the chamber 1 is shown as clear Plexiglas, and while it has roof 27, thesides 50 and others stand up past the top of the entire system.

Clearly, other embodiments of the present invention are possible inlight of the teaching and embodiments as well as the drawings herein.Those variations and limitation from embodiments are contemplated withinthe scope of the present invention and the claims which follow should beso interpreted.

Those skilled in the art to which the present invention pertains maymake modifications resulting in other embodiments employing principlesof the present invention without departing from its spirit orcharacteristics, particularly upon considering the foregoing teachings.Accordingly, the described embodiments are to be considered in allrespects only as illustrative, and not restrictive, and the scope of thepresent invention is, therefore, indicated by the appended claims ratherthan by the foregoing description or drawings. Consequently, while thepresent invention has been described with reference to particularembodiments, modifications of structure, sequence, materials and thelike apparent to those skilled in the art still fall within the scope ofthe invention as claimed by the applicant.

What is claimed is:
 1. An animal test system for use with a movingtethered test animal in an animal chamber comprising: a. a rotatingplatform positioned above the animal chamber; b. a motor for rotatingthe platform clockwise and counterclockwise; c. a plurality of lightsources for a tethered connection to the animal for delivering orreceiving a plurality of optical connections to the animal wherein thelight sources are positioned entirely on the platform; d. a digital datasystem in digital communication with and controlling the light sources,wherein the digital data system is positioned entirely on the platform.2. The system according to claim 1 wherein the digital data system is acomputer.
 3. The system according to claim 2 wherein the computer iscontrolled wirelessly.
 4. A plurality of electrical stimulation sourcesfor a tethered connection to an animal for delivering or receiving aplurality of electrical signals wherein the electrical sources anddetectors are located entirely on the platform.
 5. A digital data systemin digital communication with and controlling the electrical sources anddetectors, wherein the electrical sources and detectors are locatedentirely on the platform.